Abstract
Background aims
The Akt/mammalian target of rapamycin (mTOR) pathway in macrophages converges inflammatory
and metabolic signals from multiple receptors to regulate a cell's survival, metabolism
and activation. Although mesenchymal stromal cells (MSCs) are well known to modulate
macrophage activation, the effects of MSCs on the Akt/mTOR pathway in macrophages
have not been elucidated.
Methods
We herein investigated whether MSCs affect the Akt/mTOR complex 1 (mTORC1) pathway
to regulate macrophage polarization.
Results
Results showed that human bone marrow–derived MSCs induced activation of Akt and its
downstream mTORC1 signaling in THP-1–differentiated macrophages in a p62/sequestosome
1–independent manner. Inhibition of Akt or mTORC1 attenuated the effects of MSCs on
the suppression of tumor necrosis factor-α and interleukin-12 production and the promotion
of interleukin-10 and tumor growth factor-β1 in macrophages stimulated by lipopolysaccharide/ATP.
Conversely, activation of Akt or mTORC1 reproduced and potentiated MSC effects on
macrophage cytokine production. MSCs with cyclooxygenase-2 knockdown, however, failed
to activate the Akt/mTORC1 signaling in macrophages and were less effective in the
modulation of macrophage cytokine production than control MSCs.
Conclusions
These data demonstrate that MSCs control THP-1–differentiated macrophage activation
at least partly through upregulation of the Akt/mTORC1 signaling in a cyclooxygenase-2–dependent
manner.
Keywords
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Article info
Publication history
Published online: April 29, 2023
Accepted:
March 27,
2023
Received:
November 16,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
